interleukin-8 and Lymphoma--B-Cell

The efficacy and side effects of the second-time humanized CD19 chimeric antigen receptor (CD19-CAR) T-cell therapy after unsuccessful first-time anti-CD19-CAR T-cell therapy and subsequent ibrutinib salvage treatment were observed in patients with refractory B-cell lymphoma. In our study, 3 patients with refractory mantle cell lymphoma (MCL) and 4 patients with refractory follicular lymphoma (FL) reached stable disease (SD), partial remission (PR), or progression of disease (PD) after first-time humanized anti-CD19-CAR T-cell therapy. They received ibrutinib as a salvage treatment and kept an SD in the following 7-16 mo, but their disease progressed again during ibrutinib salvage treatment. All 7 patients received a second-time humanized anti-CD19-CAR T-cell therapy, which was the same as their first-time anti-CD19-CAR T-cell therapy. In total, 3 MCL patients and 3 FL patients reached complete response (CR) with the second-time anti-CD19-CAR T-cell therapy combined with ibrutinib, whereas 1 FL patient reached PR. There were no differences in the transduction efficiency and proliferation between the 2 instances of anti-CD19-CAR T-cell therapy. However, the second-time anti-CD19-CAR T-cell therapy led to higher peaks of anti-CD19-CAR T cells and anti-CD19-CAR gene copies, but also to higher grades of cytokine release syndrome (CRS) and more serious hematological toxicity. The successful outcome of the second-time anti-CD19-CAR T-cell therapy might suggest that the previous ibrutinib treatment improved the activities of anti-CD19-CAR T cells.

Topics: Adenine; Adult; Aged; Combined Modality Therapy; Disease Progression; Drug Resistance, Neoplasm; Female; Humans; Immunotherapy, Adoptive; Interleukin-6; Interleukin-8; Lymphoma, B-Cell; Lymphoma, Follicular; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Mantle-Cell; Male; Middle Aged; Piperidines; Receptors, Chimeric Antigen; Receptors, Interleukin-2; Remission Induction; Retreatment; Salvage Therapy; Treatment Outcome

Chronic hepatitis C carries the risk to develop mixed cryoglobulinemia (MC) and B-cell non-Hodgkin's lymphoma (B-NHL), possibly because viral antigens stimulate the host's inflammatory response via extracellular pattern recognition receptors (PRR). To clarify this issue, we studied whether recognition of hepatitis C virus (HCV) proteins by PRR is involved in the pathogenesis of HCV-associated MC or B-NHL.. Peripheral blood mononuclear cells of patients with HCV-associated B-NHL (n = 12), MC (n = 14), uncomplicated hepatitis C (n = 12), and healthy volunteers (n = 12) were incubated with the recombinant HCV proteins E2, core, and NS3 to study induction of cytokine production, stimulation of B-cell proliferation, and immunoglobulin secretion. In addition, serum levels of interleukin-6 (IL-6) were measured by ELISA.. HCV core was the only studied protein, which induced production of IL-6 and IL-8 in CD14(+) cells. IL-6 induction was mediated via Toll-like receptor 2 (TLR2) and lead to increased B-cell proliferation in vitro. TLR2 expression on monocytes and IL-6 serum concentrations were increased in all groups of HCV-infected patients compared with healthy controls and were highest in MC (P < 0.05).. Increased secretion of IL-6 via stimulation of TLR2 by HCV core protein may play a role in the pathogenesis of hepatitis C-associated MC and B-NHL.

Topics: Adult; Aged; Aged, 80 and over; Cell Proliferation; Cryoglobulinemia; Female; Hepacivirus; Hepatitis C; Humans; Interleukin-6; Interleukin-8; Leukocytes, Mononuclear; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Male; Middle Aged; Recombinant Proteins; Toll-Like Receptor 2; Up-Regulation; Viral Core Proteins

Interleukin 8 (IL-8), a member of the CXC subfamily of chemokines, is a potent inflammatory cytokine produced by many cell types in response to several stimuli. In an attempt to determine whether human B-cell IL-8 functions as an autocrine growth factor, a wide panel of B-cell lines derived from patients with AIDS-associated B-cell lymphomas (AABCL) (n = 5) and from non-AABCLs (n = 8) was studied for expression of IL-8, IL-8 Receptor type A (IL-8R), and secretion of IL-8 protein. Using RT-PCR and Northern Blot analysis, we were able to observe IL-8 expression ubiquitously. However, IL-8R expression was seen only in EBV negative (4 out of 7) B-cell lines. EBV and HIV-1 activated B-cell line; HBL-1, was the major secretor of IL-8. Our results demonstrate that IL-8 is expressed in malignant B-cell phenotypes that correspond to a narrow window in the B-cell differentiation pathway (pre-B, early-B, and intermediate-B) as well as in normal CD19-enriched B-cells. Furthermore, IL-8 autocrine loops were not evident since IL-8R was detected only in cell lines that did not secrete IL-8 protein.

Topics: B-Lymphocytes; Base Sequence; Blotting, Northern; Burkitt Lymphoma; Cloning, Molecular; DNA Primers; Glyceraldehyde-3-Phosphate Dehydrogenases; Humans; Interleukin-8; Lymphoma, AIDS-Related; Lymphoma, B-Cell; Receptors, Interleukin-8A; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; RNA, Neoplasm; Tumor Cells, Cultured

Physiologically, B-lymphocytes are not present in the skin. Even in pathological situations they rarely occur. In contrast, primary cutaneous B-cell lymphomas (CBCL) are characterized by proliferation of B lymphocytes within the skin. This suggests the existence of a certain microenvironment supporting homing and expansion of clonal B cells. Cytokines were demonstrated to be involved in the pathogenesis of cutaneous lymphomas of T-cell origin. Cytokine expression in cutaneous B-cell lymphoma lesions, however, has not been investigated so far. Therefore, the mRNA level of several cytokines was analyzed in biopsies from 7 patients with CBCL and compared to pleomorphic T-cell lymphoma (n = 6), psoriasis (n = 9), and healthy skin (n = 7), using a competitive RT-PCR approach. An overexpression of TNF-alpha, IL-10, and IL-6 was found. Enhanced IL-8 mRNA expression was detected in 2/7 cases. The overexpression of IL-6 and IL-10 in CBCL might be of particular importance, since these cytokines are considered to support B-cell growth. Additionally, the overexpression of IL-10 may contribute to tumor progression since this immunosuppressive cytokine might be involved in downregulation of immunological tumor surveillance, in part by inhibiting type 1 cytokine formation. In fact, we did not detect IFN-gamma and IL-2 expression. Taken together, we found a cytokine pattern in CBCL lesions which might contribute to tumor B-cell growth.

Topics: Adult; Cytokines; Gene Expression; Humans; Immunohistochemistry; Inflammation Mediators; Interleukin-10; Interleukin-6; Interleukin-8; Lymphoma, B-Cell; RNA, Messenger; RNA, Neoplasm; Skin Neoplasms; Tumor Necrosis Factor-alpha

Monocyte chemotactic protein 1 (MCP-1) and interleukin 8 (IL-8) are small, inducible proteins with chemotactic activity for specific subsets of leucocytes. The possibility that MCP-1 and IL-8 are produced in tissues involved by Hodgkin's disease, thus contributing to the inflammatory-type background of the lesion, was investigated.. The presence of RNA transcripts for MCP-1 and IL-8 was investigated in biopsy samples of 24 cases of Hodgkin's disease, 17 non-Hodgkin's malignant lymphomas, 30 solid tumours, and 30 histologically normal tissues by means of reverse transcription-polymerase chain reaction (RT-PCR)/Southern blot analysis.. MCP-1 expression was detected in 23 of 24 cases of Hodgkin's disease, in seven of 17 cases of B cell non-Hodgkin's lymphoma, and in seven of 14 cases of reactive lymphoid hyperplasia. IL-8 was present in six of 14 cases of Hodgkin's disease, and was seen only rarely in B cell non-Hodgkin's lymphoma and in reactive lymphoid tissues. MCP-1 and IL-8 RNA transcripts were detected in 13 of 25 carcinomas originating from the lung, breast, thyroid, and ovary.. These findings are consistent with the possibility that MCP-1 and IL-8 are two additional cytokines involved in the pathogenesis of Hodgkin's disease.

Topics: Blotting, Southern; Chemokine CCL2; Female; Hodgkin Disease; Humans; Interleukin-8; Lymphoma, B-Cell; Neoplasm Proteins; Neoplasms; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger